This proposal represents a second revision of a competing renewal of ROI HL 42456-O3 entitled, "Antihypertensive Therapy and Primary Cardiac Arrest". Unexpected findings from the Cardiac Arrhythmia Suppression Trial--an adverse effect on mortality of two antiarrhythmic drug therapies---have heightened concerns that other drug therapies may increase the risk of primary cardiac arrest. To determine whether treatment with antidepressant, anticonvulsant, and antiarrhythmic drugs- therapies that have the potential for proarrhythmia-increase the risk of primary cardiac arrest, we propose to conduct a population-based case- control study nested within a cohort of patients who receive medical care at a large pre-paid Health Care Plan in Seattle (Washington). Cases are patients who had a primary cardiac arrest between 1977 to 1994. Controls are a stratified random sample of patients, frequency-matched to cases by age, gender, calendar-year, and known heart disease. Treatment with drugs will be assessed through a computerized pharmacy database. Ambulatory-care medical records will be reviewed to assess clinical characteristics, including the indication for therapy, the severity of heart disease, co- existing morbidity, and other risk factors. For both antidepressant and anticonvulsant drugs, analyses will be stratified by known heart disease, because the risk of treatment may be particularly large among patients with known heart disease. For antiarrhythmic drugs, analyses will be restricted by a single, current indication for the therapy--maintenance of sinus rhythm among patients with chronic atrial fibrillation; and, by the availability of a prior echocardiogram, in order to control for the type and severity of underlying heart disease. After adjustment for potential confounders, we will estimate the risk of primary cardiac arrest among patients treated with a drug as compared to patients who are not treated. We also will examine the relative safety of: 1) drugs within the same therapeutic class; and, 2) the dosage schedule for specific drugs. In addition, we will determine if concurrent treatment with other drugs that alter cardiac conduction or morbidity that alters drug disposition influences the risk among patients treated with a drug therapy. Although we expand the scope of research, the proposed research builds directly upon resources and methods developed during the initial funding period.